Programmed cell death
Cell death from internal events, crucial for development and homeostasis.
Programmed cell death (PCD), also called cell suicide or cellular suicide, is the death of a cell resulting from internal events such as apoptosis or autophagy. It is a biological process that typically confers an advantage during an organism's lifecycle, for example in the separation of fingers and toes during human embryonic development. PCD serves fundamental functions in both plant and animal tissue development.
The concept of programmed cell death was first introduced in 1964 in the context of insect tissue development, predating the term "apoptosis" by about eight years. While PCD has become the general term for all genetically driven cell death, its definition has caused some confusion, leading to refined mechanistic and evolutionary definitions. Early mechanistic insight came from studying the BCL2 gene, which was found to promote cancer not by stimulating cell growth, but by preventing lymphoma cells from undergoing suicide. The importance of PCD was recognized with the 2002 Nobel Prize in Physiology or Medicine.
PCD encompasses several types. Apoptosis, or Type I cell death, involves characteristic changes such as cell shrinkage, membrane blebbing, nuclear fragmentation, and DNA fragmentation. It can proceed through an extrinsic pathway, triggered by receptor-ligand interactions like FAS or TNF-alpha, or an intrinsic pathway, initiated by cell damage such as DNA damage or UV exposure. The intrinsic pathway operates through mitochondrial sensors and proteins like BAX and BAK, which form pores in the mitochondrial membrane to release cytochrome c, ultimately activating executioner caspases. Autophagic cell death, or Type II, is marked by large vacuoles that consume organelles before the nucleus is destroyed. While necrosis was long considered a non-physiological process caused by external injury, a programmed form called necroptosis was recognized in the 2000s as an alternative backup when apoptosis is blocked by factors like viruses. Other regulated necrosis types have since been discovered, sharing signaling events with both necroptosis and apoptosis.
- field
- Cell biology
- known_for
- Concept of programmed cell death, including apoptosis, autophagy, and necroptosis
- types
- Apoptosis (Type I), Autophagic cell death (Type II), Necroptosis
Lore & Background
Programmed cell death (PCD) encompasses several distinct forms, including apoptosis and autophagy, and is a biological process that typically benefits the organism during its lifecycle. In developing human embryos, for instance, the separation of fingers and toes occurs because cells in the webbing between them undergo apoptosis. PCD is fundamental to tissue development in both plants and animals. Apoptosis, also known as Type I cell death, involves characteristic morphological changes such as cell shrinkage, membrane blebbing, nuclear fragmentation, and DNA fragmentation. It can be triggered via two pathways: the extrinsic pathway, which involves receptor-ligand interactions (e.g., FAS or TNF-alpha) and leads to caspase activation, or the intrinsic pathway, which originates from cell damage (like DNA damage or UV exposure) and is mediated by mitochondrial proteins such as BAX and BAK, culminating in cytochrome c release and apoptosome formation. Autophagic cell death, or Type II, is characterized by the formation of large vacuoles that sequentially consume organelles before the nucleus is destroyed. While necrosis was long considered a non-physiological response to external injury, a regulated form called necroptosis was recognized in the 2000s as an alternative PCD pathway, potentially serving as a backup when apoptosis is blocked by viruses or mutations. Other regulated necrosis types have since been discovered, sharing signaling events with both necroptosis and apoptosis. The concept of PCD was first introduced in 1964 by Lockshin and Williams in the context of insect tissue development, predating the term "apoptosis" by about eight years.
Reader's Guide
Robert Horvitz, and John E. Sulston. The field encompasses multiple pathways: apoptosis (Type I), autophagic cell death (Type II), and necroptosis, a form of programmed necrosis recognized in the 2000s. Necroptosis can serve as a backup to apoptosis when apoptosis signaling is blocked by viruses or mutations. Other regulated necrosis forms have since been discovered, sharing signaling events with necroptosis and apoptosis. The balance between mitosis and apoptosis depends on signals from growth or survival factors. Autophagy and apoptosis are connected both positively and negatively, with extensive crosstalk; for example, Bcl-2 inhibits Beclin-1-dependent autophagy, functioning as both a pro-survival and anti-autophagic regulator.
Did You Know?
- BCL2, an oncogene in follicular lymphoma, promotes cancer by stopping lymphoma cells from killing themselves.
- Necroptosis was recognized in the 2000s as a programmed form of necrosis that can serve as a backup to apoptosis.
- Autophagy is generally activated by nutrient deprivation but is also associated with development, differentiation, neurodegenerative diseases, stress, infection, and cancer.
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